December 21, 2020 – The European Haemophilia Consortium (EHC) has learned that uniQure announced that its haemophilia B gene therapy programme, including the pivotal, phase III HOPE-B study, has been placed on hold by the US Food and Drug Administration (FDA). The clinical hold was initiated following the submission of a safety report in mid-December relating to the possibility of a serious adverse event associated with a preliminary diagnosis of hepatocellular carcinoma (HCC), a form of liver cancer, in one patient in the HOPE-B trial that was treated with etranacogene dezaparvovec (AMT-061) in October 2019.

The male patient has multiple risk factors associated with the development of liver cancer including a history of hepatitis C (treated prior to enrollment), exposure to hepatitis B virus, evidence of non-alcoholic fatty liver disease and has advanced age. Chronic infections with hepatitis B and C have been associated with approximately 80% of HCC cases[1]. The liver lesion was detected during a routine abdominal ultrasound conducted as part of the required study assessments in patients at one-year post-dosing. A full surgical resection of the lesion is scheduled this week that will allow for confirmation of the diagnosis. uniQure has started a plan for comparison of the integration of the gene therapy in the lesion and to healthy liver tissue to determine if there is an association with the gene therapy.

No other cases of HCC have been reported in uniQure clinical trials conducted in more than 100 patients in haemophilia B and other indications, with some patients dosed more than 10 years ago, the company has stated.

The company noted that the patient dosing for the HOPE-B phase III was completed and that there was no plan to enrol any additional patient. uniQure is working closely with the FDA and their advisors to conduct a thorough investigation into the cause of this event, which they expect to complete in early 2021. All patients enrolled in the HOPE-B trial will continue to be monitored by their care teams as the company gathers additional information as rapidly as possible. The company does not anticipate any impact on its regulatory submission timeline for the haemophilia B programme as a result of this clinical hold.

The full press release is available here.

[1] El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012 May;142(6):1264-1273.e1. doi: 10.1053/j.gastro.2011.12.061. PMID: 22537432; PMCID: PMC3338949.